菲律宾人CYP2C9基因单核苷酸多态性及其与COX-2抑制剂术后疼痛缓解的关系

International journal of molecular epidemiology and genetics Pub Date : 2020-10-15 eCollection Date: 2020-01-01
Leland Arden T Ustare, Karen G Reyes, Marie Angelica G Lasac, Salvador E Brodit, Michael O Baclig
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引用次数: 0

摘要

CYP2C9基因编码一种酶,参与包括塞来昔布在内的多种药物的代谢。本研究调查了菲律宾手术患者中CYP2C9*1、CYP2C9*2和CYP2C9*3等位基因的频率和基因型,并确定CYP2C9多态性与COX-2抑制剂术后疼痛缓解的关系。采用数值评定量表(0-10)在手术第24小时和第48小时对塞来昔布的反应进行评定。实时荧光定量PCR检测CYP2C9等位基因。菲律宾人CYP2C9*1和CYP2C9*3等位基因频率分别为99%和1%,与其他东亚人相似。未检测到CYP2C9*2等位基因。CYP2C9*1/*1和CYP2C9*1/*3基因型频率分别为98%和2%。CYP2C9*1野生型等位基因患者术后24小时的平均疼痛评分为2.57±1.03,48小时的平均疼痛评分为0.67±0.61。2例CYP2C9*1/*3基因型中间代谢物患者术后24小时和48小时的平均疼痛评分分别为2.5±0.71和0.5±0.71。在本研究中观察到CYP2C9多态性的低频率,这种模式与除印度人外的其他亚洲人相似,远低于高加索人。我们的研究结果表明,CYP2C9基因分型在菲律宾人中并不常规需要,但在混合种族中必须考虑。因此,从这些数据中得出了更个性化的治疗策略,从而获得了良好的临床结果和更少的药物不良反应。
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Single nucleotide polymorphisms on CYP2C9 gene among Filipinos and its association with post-operative pain relief via COX-2 inhibitors.

CYP2C9 gene encodes an enzyme involved in the metabolism of a wide variety of drugs which include celecoxib. This study investigated the frequencies of the alleles and genotypes of CYP2C9*1, CYP2C9*2, and CYP2C9*3 among Filipinos who underwent surgery, and to determine the association of CYP2C9 polymorphisms with post-operative pain relief via COX-2 inhibitors. Response to celecoxib was determined using the numerical rating scale (0-10) on the 24th and 48th hour of surgery. The CYP2C9 alleles were detected by real-time PCR. For CYP2C9*1 and CYP2C9*3, the allele frequencies among Filipinos were 99% and 1% respectively, which is similar with other East Asians. CYP2C9*2 alleles were not detected. The frequencies of CYP2C9*1/*1 and CYP2C9*1/*3 genotypes were 98% and 2% respectively. At 24 hours post-surgery, the average pain score was 2.57 ± 1.03, while on 48 hours post-surgery, the average pain score was 0.67 ± 0.61 among those who have the wild-type CYP2C9*1 allele. The average pain score on the 24th and 48th hour post-operatively was observed to be 2.5 ± 0.71 and 0.5 ± 0.71 respectively among two patients classified as intermediate metabolizer carrying the CYP2C9*1/*3 genotype. Low frequencies of CYP2C9 polymorphisms were observed in the present study, this pattern was similar with other Asians except Indians, and considerably lower than Caucasians. Our results suggest that CYP2C9 genotyping is not routinely needed for Filipinos but must be considered among mixed races. Consequently, a more personalized therapeutic strategy was derived from these data, resulting in good clinical outcomes and less adverse drug effects.

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